Abstract
Abstract: :
Purpose: In age related macular degeneration (ARMD) retinal pigment epithelium (RPE) apoptosis leads to loss of photoreceptors. Factors of RPE apoptosis are oxidative stress and zinc deficiency as well as lipofuscin deposition. Because in different cells exposure to exogenous AGEs is able to induce oxidative stress we tested the mechanisms of AGE induced stress. Methods: Human RPE cells (ARPE) were incubated with defined AGEs and with the reactive intermediate of AGE-formation glyoxal. The distribution and motility of intracellular microvesicles (lysosomes), intracellular pH (pHi), mitochondrial potential and membrane integrity was analyzed. Results: In RPE cells AGEs as well as glyoxal induce velocity reduction and clustering of intracellular microvesicles (lysosomes), pHi and mitochondrial potential reduction and signs of apoptosis like chromatin condensation and membrane permeability changes. Conclusion: We found that AGEs can contribute to the accumulation of lipofuscin deposits after cis-retinal phagocytosis by impairment of vesicular transport. High AGE-formation can induce RPE cell apoptosis. This study opens new prospects in prevention of RPE cell loss in ARMD by AGE-breakers as well as antioxidative substances.
Keywords: 567 retinal pigment epithelium • 561 retinal degenerations: cell biology • 341 cell death/apoptosis